The objectives of the REDS-III program are to ensure safe and effective blood banking and transfusion medicine practices through a comprehensive, multi-targeted strategy involving basic, translational, and clinical research to improve the benefits of transfusion while reducing its risks. Improving blood component safety and availability in the U.S. and internationally through the conduct of epidemiologic, survey, and laboratory studies is the cornerstone of the REDS program. Transfusion therapy is the most commonly employed, and, arguably, one of the least understood medical procedures in the U.S. affecting about five million recipients annually. This research program is not only critical to public health in the U.S. but also to countries struggling with the HIV epidemic where blood safety and availability are major concerns. The REDS-III program is comprised of one Data Coordinating Center (DCC), one Central Laboratory, four domestic hubs, and three international collaborative programs involving U.S. investigators and investigators at international blood centers. The REDS-III program will target the following blood banking and transfusion medicine areas: donor targeted strategies; blood banking; transfusion practices in adult patients; and education and training. The goal of the International program is to address scientific questions to improve the safety and adequacy of the blood supply in selected low or middle income countries affected by the HIV/AIDS epidemic. The REDS-III international sites shall conduct epidemiologic, laboratory, and survey research primarily on blood donors with a major research focus on reducing and preventing the transmission of HIV/AIDS and other known and emerging infectious agents through transfusion. Studies in transfusion recipients may also be conducted. The major objectives of the research in the international program are: 1) assess and monitor the prevalence and incidence of HIV-1, HIV-2 and other existing as well as newly discovered infectious agents that pose a threat to blood safety; 2) assess risks of transfusion-transmitted infections; 3) assess the impact of existing and new blood donor screening methodologies on blood safety and availability; 4) evaluate characteristics and behaviors of blood donors including risk factors for acquiring HIV and other blood-borne agents; and 5) evaluate the donation process for ways to improve the safety and adequacy of the blood supply. Some studies may also address transfusion recipient safety concerns such as evaluating non-infectious transfusion risks (e.g., alloimmunization) and ways to reduce their occurrence.